The pathogenesis of pyelonephritis will be investigated. We will attempt to elucidate the mechanism of mediation of experimental enterococcal pyelonephritis when bacteria are no longer present. It will be determined whether lymphocytes from pyelonephritic rats have acquired antikidney activity. Studies in vivo will be to determine if lymphocytes from pyelonephritic animals will produce a graft versus host response when injected under the kidney capsule of normal inbred recipients. The effect of lymphocytes from pyelonephritic animals on normal kidney tissue in vitro will be studied. Lymphocytic antikidney activity will also be studied in vitro by antigen migration inhibition and stimulation techniques. To determine whether the mediation of pyelonephritis might be via antigen in the kidney, enterococcal antigen will be deposited in the kidneys of normal rats and kidneys will be examined at intervals histologically for evidence of a reaction. The effect of immunosuppression on persistence of pyelonephritis in rats cured of the infection by appropriate antibiotic therapy will be studied. Other studies will relate to pathogenesis of Escherichia coli pyelonephritis. The effects of deposition of galactitol in mouse kidney on pathogenesis of the E. coli pyelonephritis will be evaluated. We will study the relation between iron metabolism and virulence in this model. It will be determined whether patients with chronic pyelonephritis manifest delayed hypersensitivity to kidney tissue and to E. coli. It will be investigated, with the use of the mouse model, whether human E. coli isolates from kidney are more virulent than those isolated from the bladder.